You are here:
EMERGING ISSUES RELATED TO ENDOCRINE DISRUPTING CHEMICALS AND ENVIRONMENTAL ANDROGENS AND ANTIANDROGENS
Citation:
Gray Jr., L. E., C R. Lambright, L G. Parks, R. W. Tyl, E. F. Orlando, L. J. Guillette, C J. Wolf, J. C. Seely, T. Y. Chang, V S. Wilson, A. Hotchkiss, AND J S. Ostby. EMERGING ISSUES RELATED TO ENDOCRINE DISRUPTING CHEMICALS AND ENVIRONMENTAL ANDROGENS AND ANTIANDROGENS. Chapter II, Manfred Metzler (ed.), Handbook for Environmental Chemistry. Endocrine Disruptors. Springer Verlag, 209-248, (2002).
Description:
Wildlife populations from contaminated ecosystems display a variety of reproductive alterations including cryptorchidism in the Florida panther, small baculum in young male otters, small penises in alligators, sex reversal in fish, and altered social behavior in birds. In some cases, clear cause and effect relationships exist between exposure to endocrine disrutping chemicals (EDCs) and adverse effects in fish, wildlife and domestic animals. The formation of biologically plausible hypotheses regarding toxicant-induced disruption of reproduction can be facilitated by definitive mechanistic rodent studies. To this end, we have investigated the in vivo and in vitro effects of suspect antiandrogenic and dioxin-like substances. In vivo studies examined short-term effects, effects on puberty and toxicant-induced alterations of rat sexual differentiation. We utilize short-term in vivo and in vitro assays (receptor binding, transfected cell and steroidogenesis assays) in order to confirm the suspected mechanism of action. To date, in vitro and in vivo studies have identified several antiandrogenic toxicants including vinclozolin, procymidone, linuron, several phthalate esters and p,p' DDE, all of which alter male rat sex differentiation. 2,3,7,8 tetrachlorodibenzo-p-dioxin (TCDD) and the TCDD-like congener PCB 169 affect both male and female offspring, inducing dramatic reductions in ejaculated sperm numbers at low dosage levels. In utero exposure to antiandrogenic and TCDD-like chemicals result in profiles of effects in the offspring that are pathognomonic for each mechanism of action. Mechanistic information from rodent studies using dosing regimes that produce relevant toxicant tissue levels, coupled with an understanding of the endocrine factors regulating reproductive development in the species of concern, can enhance our ability to predict the effects of endocrine disrupting chemicals on human and wildlife reproduction. For some EDCs (i.e. PCBs, PCDDs, PCDFs or p,p' DDE), developmental effects are seen in rats using dosing regimes that produce fetal exposure levels that appear to be within the reported range of some segments of the human population.